Mechanisms of cell regulation - proteolysis, the big surprise

Precise regulation of cellular processes is essential for life. Regarding proteins, many regulatory mechanisms were explored over the years, such as posttranslational modifications (e.g., phosphorylation), enzyme activation or inhibition by small molecules, and modulation of protein-protein interactions. Complete removal of a protein via proteolysis as a regulatory mechanism, however, was denied for a long time, mainly due to economical considerations. Scientists could not believe that a protein which is synthesized at the expense of a lot of energy could be destroyed again. Here, we discuss the landmark discoveries and the use of yeast as a eukaryotic model organism that finally paved the way for our current understanding of proteolysis as an essential regulatory principle in the cell.